RESUMO
BACKGROUND: Herpes simplex type 1 (HSV-1) is widely distributed throughout the world's population. The virus spreads through direct contact with an infected individual. After primary infection, the virus remains in a latent state, and the recurrence of herpetic lesions is common. Standard treatment is performed with nucleoside analogues, but the selection of resistant strains have occurred, thus requiring the continual search for new antiviral agents. Plant extracts, fractions, and isolated compounds are a good source for studying possible antiviral compounds. HYPOTHESIS: Among plants with antiviral activity, the crude extract of aerial parts of Tanacetum parthenium (L.) Sch.Bip. (Asteraceae) have previously shown to inhibit HSV-1 infection in vitro. METHODS: The present study investigated the chemical composition of a crude hydroethanolic extract (CHE) of T. parthenium, and in vivo safety and therapeutic efficacy against HSV-1 infection. RESULTS: Liquid chromatography-mass spectrometry showed that the CHE was composed of phenolic acids (chlorogenic acids) and sesquiterpene lactones (parthenolide). Acute and subchronic toxicity and genotoxicity tests in vivo showed that oral CHE administration did not result in signs of toxicity, with no genotoxic potential. The CHE was also safe for topical administration, in which no irritation of the epidermis was observed in treated animals. Tests of topical and oral therapeutic efficacy showed that the CHE was effective against HSV-1 infection. Topical administration was the most effective, the results for which were comparable to acyclovir. CONCLUSION: These findings indicate that the CHE from aerial parts of Tanacetum parthenium has in vivo anti-HSV-1 activity and is safe for oral and topical application.
Assuntos
Antivirais/toxicidade , Antivirais/uso terapêutico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/efeitos dos fármacos , Extratos Vegetais/toxicidade , Tanacetum parthenium/química , Tanacetum parthenium/toxicidade , Animais , Antivirais/farmacologia , Camundongos , Modelos Animais , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
The mutagenic potential of a crude extract of Parthenium hysterophorus L. was assessed in the Salmonella/microsome (Ames) assay and the mouse bone marrow micronucleus test. Results in the bacterial mutagenicity assay were negative for the five strains employed, e.g. TA 1535, TA1537, TA 98, TA 100 and TA 102, while cytotoxicity was evident in all cases at 5000 microg per plate, the highest concentration assayed. A decrease in toxicity was observed with exogenous mammalian metabolic activation (S9) or glutathione (5 micromol per plate). When mutagenicity was monitored after column chromatography fractionation of the crude, fraction 1 was mutagenic in strain TA 98 (+S9). Besides, cytotoxicity was found in fraction 5, where parthenin was eluted. The micronucleus test was negative in mice upon oral administration, at doses up to 96 mg of crude per kg. Bone marrow toxicity was not observed. The crude extract exhibited some in vitro pro-oxidant activity. It also inhibited lipid peroxidation (IC(50)=4.1 microg/ml) but failed to act as .OH scavenger.